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  • Original Paper
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Granulocytic differentiation of myeloid progenitor cells by p130, the retinoblastoma tumor suppressor homologue

Oncogene volume 18, pages 6209–6221 (1999)Cite this article

Abstract

The retinoblastoma protein (pRB) and the related pocket proteins, p107 and p130, play crucial roles in mammalian cell cycle control. Recent studies indicate that these pocket proteins are also involved in cellular differentiation processes. We demonstrate in this work that the pRB-related p130 selectively accumulates during the in vitro differentiation of the myeloid progenitor cell, 32Dcl3, into granulocyte in response to granulocyte-colony stimulating factor (G-CSF). This G-CSF-dependent granulocytic differentiation is blocked by the adenovirus E1A oncoprotein, which binds to and inactivates the pRB family of pocket proteins including p130. Furthermore, enforced overexpression of p130 but not pRB inhibits the myeloid cell proliferation that is concomitantly associated with granulocytic differentiation morphologically characterized by nuclear segmentation. However, simple G1-cell cycle arrest induced by cytokine deprivation or ectopic overexpression of the p27 cyclin-dependent kinase inhibitor, or inhibition of E2F activities by dominant negative DP-1 is not sufficient to trigger granulocytic differentiation. The differentiation-promoting activity of p130 in myeloid cells requires both the pocket domain and the spacer domain. Our results indicate that the pRB-related p130 plays a critical role in myeloid cell differentiation and suggest that coupling of cell cycle exit with the cellular differentiation program may be specifically achieved by p130.

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Acknowledgements

We thank Dr L Yamasaki for reading of the manuscript. We also thank Dr K Ando for providing 32Dcl3 cells; Dr P Whyte for mutant p130 cDNA; and Dr T Nakamura for technical assistance. This work was supported by Research Grants from the Princess Takamatsu Cancer Research Fund and from Nippon Boehringer Ingelheim Co., Ltd.

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Authors and Affiliations

  1. Department of Viral Oncology, Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-Ku, Tokyo, 170-8455, Japan

    Akio Mori, Hideaki Higashi, Yutaka Hoshikawa & Masanori Hatakeyama

  2. Department of Hematology and Oncology, Hokkaido University School of Medicine, Sapporo, 060-8638, Japan

    Masahiro Imamura

  3. Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, 060-8638, Japan

    Masahiro Asaka

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  1. Akio Mori
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  2. Hideaki Higashi
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Mori, A., Higashi, H., Hoshikawa, Y. et al. Granulocytic differentiation of myeloid progenitor cells by p130, the retinoblastoma tumor suppressor homologue. Oncogene 18, 6209–6221 (1999). https://doi.org/10.1038/sj.onc.1203044

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